Parkinson's disease (PD) is a prevalent, heterogeneous disorder with a complex, multifactorial etiology. The syndrome affects multiple systems with motor and non-motor features. In the past decade, many genes and specific mutations contributing to disease risk have been identified. In the Arab-Berber population of Tunisia in North Africa the burden of genetically-defined PD is especially high. In this project the NINDS Udall Center at MCJ and the National Institute of Neurology in Tunis aim to share clinical, genetic, pathological and scientific expertise, to work towards the common goal of defining the natural history of PD, while building research capacity in Tunisia. Our proposal has five main aims: 1) To build database infrastructure and informatic resources (with the support of Zaah Technologies);2) Clinical assessment of parkinsonism in research subjects;3) Clinical assessment of non-motor disability;4) Assessment of pedigrees with familial parkinsonism, and;5) Genetic assessment of known and novel genes for parkinsonism. Together we intend to foster longitudinal clinical and genetic research that was initiated by GlaxoSmithKline, but is no longer supported. Research capacity, resources and expertise in Tunisia at the National Institute of Neurology are to be building about a pragmatic need, developing ocal expertise and resources. Nevertheless, the insights gained in PD are likely to be of universal benefit. The training provided and infrastructure developed in Tunis may also facilitate research in other prevalent neurological disorders. PUBLIC HEALTH RELEVANCE: The work proposed is a natural history study of Parkinson's disease (PD). Our objective is to: 1) build research capacity, resources and expertise in the National Institute of Neurology, Tunis, and;2) develop cross- sectional research initiated by GlaxoSmithKline into a collaborative, longitudinal study of the natural history of PD, and;3) forge a close collaboration between a NINDS Udall Center, the Departments of Neurology and Neuroscience at MCJ with the National Institute of Neurology in Tunis. We aim to share clinical, genetic, pathological and scientific expertise, our research data and experience. While the research proposed meets local needs in Tunisia, the research capacity and insights gained in PD will be of universal benefit. The training provided and infrastructure developed in Tunis may also facilitate research in other prevalent neurological disorders.